Parasitic Infection With Toxoplasmosis May Be Linked To Parkinson’s & Alzheimer’s Disease

MedicalResearch.com Interview with:

Under a magnification of 900X, this hematoxylin and eosin-stained (H&E) photomicrograph of a brain tissue specimen revealed a case of neurotoxoplasmosis in a patient who had also been diagnosed with multiple myeloma. Note the Toxoplasma gondii tissue cyst, within which bradyzoites could be seen developing. CDC Image

Rima McLeod, M.D., F.A.C.P, F.I.D.S.A
Professor of Ophthalmology and Visual Sciences,Pediatrics (Infectious Diseases), and The College,
Director, Toxoplasmosis Center,
Senior Fellow,Institute of Genomics, Genetics and Systems Biology, Member, Commitees on Immunology, and Molecular Medicine and Pathogenesis,
Member Global Health Center, Affiliate CHeSS;
Attending Physician, Chicago Medicine,
The University of Chicago

MedicalResearch.com: What is the background for this study?

* One third of humans are infected lifelong with the brain-dwelling, protozoan parasite, Toxoplasma gondii.
* Approximately fifteen million of these have congenital toxoplasmosis.
* The parasite interconverts between slow-growing, encysted bradyzoites and rapid-growing tachyzoites.
* In mice, T. gondii creates a chronic intra-neuronal infection and an inflammatory process.
* Mice with acute and chronic infection have alterations in neurotransmitters, memory, seizures, and neurobehavior.
* Some epidemiologic-serologic studies show associations between seropositivity for T. gondii and human neurologic diseases, for example, Parkinson’s and Alzheimer’s diseases.
* Although neurobehavioral disease is associated with seropositivity, causality is unproven.
* Serologic studies of humans with diverse genetics are not optimal to detect strong associations or directionality.
* Epidemiologic associations also do not reveal parasite-modulated gene networks in human brain that could provide insights into how to cure and prevent resultant diseases.
* We need integrative approaches to examine relationships between brain parasitism and other brain diseases, to provide a foundation to identify key pathways and molecules for drug and vaccine design
* To address these problems, we considered two central questions: (i) If chronic brain parasitism associates with other neurologic diseases, what are they? And (ii) Which macromolecular networks are modulated by the parasite in human brain that lead to neuropathology which could underpin and facilitate design of treatments?
* We hypothesized that a systems approach integrating multiple levels of host parasite interactions might resolve these questions.
* To better understand what this parasite does to human brains, we performed a comprehensive systems analysis of the infected brain.  Continue reading

Diabetes Medication Exenatide Shows Promise In Treating Parkinson’s Disease

MedicalResearch.com Interview with:
Dr Dilan Athauda MRCP
Sobell Department of Motor Neuroscience and Movement Disorders
UCL Institute of Neurology & The National Hospital for Neurology and Neurosurgery
London

MedicalResearch.com: What is the background for this study?

Response: Exenatide is a synthetic version of a naturally occurring protein – exendin-4 – that was originally discovered by Dr John Eng in the early 1990’s in the saliva of the Gila Monster, a venomous lizard native to the Southwestern United states. He and his team were looking for bio-active peptides in insect and lizard venom that could be useful for people with Type 2 diabetes. They discovered that exendin-4 was extremely similar to a human hormone called Glucagon-like peptide-1 (GLP-1).  In humans, GLP-1 is secreted after you eat a meal to stimulate insulin secretion (and inhibit glucagon production) of which the end result is a lowering of blood sugar. Unfortunately human GLP-1 is rapidly broken down by a circulating enzyme called dipeptidyl peptidase IV (DPP-IV) and its effects only last minutes.

Importantly, it was discovered that exendin-4 is naturally resistant to the actions of this enzyme, meaning it’s effects on blood sugar control lasts much longer in the body.  These properties made it very attractive to people trying to treat people with Type 2 diabetes and following many successful randomised controlled trials of patients with Type 2 diabetes in 2005, exenatide was approved for use as a treatment.  During this time, work led by Nigel Greig’s group at the NIA showed that first evidence that exendin-4 had neuroprotective properties, and could protect neurons from a variety of stresses and could also improve growth and rescue degenerating cells. Over the next few years, various groups used exendin-4 in a variety of animal toxin models of Parkinson’s disease and showed that exendin-4 could halt the progression of Parkinsonism and prevent cell death in these models through beneficial effects on inflammation, mitochondrial function and cell survival.

Based on this encouraging pre-clinical data, Professor Foltynie supervised the first small, “open-label”, human trial of exenatide in patients with Parkinson’s disease.  The team found that patients treated with exenatide for 1 year (in addition to their usual medication) had less decline in their motor symptoms when assessed without their medication compared to the control group (just on their usual medication) and this advantage over the control group was still present 1 year after stopping the exenatide injections.  However, this trial was open-label – patients knew they were getting a (potentially beneficial) experimental therapy and so we couldn’t exclude the fact that placebo effects were explaining some of the results we saw.

As a result of the potentially beneficial results seen in this small open label trial we carried out a double-blind, placebo controlled trial.

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Extended-Release Amantadine Reduces Dyskinesia in Parkinson’s Disease

MedicalResearch.com Interview with:
Rajesh Pahwa MD
Department of Neurology
University of Kansas Medical Center, Kansas City, KS,

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Dyskinesia are one of the major unmet needs in Parkinson Disease patients. At the present time there are no approved medication for dyskinesia, however immediate release amantadine is used in PD patients with dyskinesia. ADS-5102 is a long acting, extended release capsule formulation of amantadine HCl administered once daily at bedtime. This study investigated the safety, efficacy and tolerability of ADS-5102 in Parkinson’s disease (PD) patients with levodopa-induced dyskinesia.

This was a randomized, double-blind, placebo-controlled study of Parkinson’s disease patients with levodopa-induced dyskinesia. In total, 126 patients were randomized to placebo or 274 mg ADS-5102 administered orally at bedtime. ADS-5102 was associated with a significant reduction in dyskinesia at 12 weeks compared with placebo, as measured by the mean change in Unified Dyskinesia Rating Scale (treatment difference, –7.9; P =.0009). OFF time was significantly reduced in ADS-5102 patients compared to placebo (treatment difference -0.9 hours, p=.017).

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Vagotomy May Point To Gut Origin of Parkinson’s Disease

MedicalResearch.com Interview with:

Karin Wirdefeldt, MD, PhD</strong> Associate professor Karolinska Institutet Stockholm, Sweden

Dr. Wirdefeldt

Karin Wirdefeldt, MD, PhD
Associate professor
Karolinska Institutet
Stockholm, Sweden

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: It has been hypothesized that Parkinson’s disease may start in the gut and spread to the brain via the vagal nerve. We found that people who had a truncal vagotomy (ie, the nerve trunk fully resected) at least 5 years earlier were less likely to develop Parkinson’s disease compared to people without vagotomy or people who had a selective vagotomy (ie, only branches of the nerve resected).

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Diabetes Drug May Slow Progression of Parkinson’s Disease

MedicalResearch.com Interview with:

Patrik Brundin, M.D., Ph.D. Director, Center for Neurodegenerative Science Van Andel Research Institute

Dr. Patrik Brundin

Patrik Brundin, M.D., Ph.D.
Director, Center for Neurodegenerative Science
Van Andel Research Institute

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The investigational drug at the heart of our study, MSDC-0160, has been in development to treat type 2 diabetes by improving cellular metabolism.

In Parkinson’s, reductions in cellular metabolism slow down vital housekeeping processes that clear out toxic proteins that otherwise accumulate with age. If these proteins aren’t removed, they clump together, leading to the damage and cell death that causes Parkinson’s hallmark symptoms, such as rigidity and tremor. MSDC-0160 helps keep these housekeeping processes working, ultimately protecting the brain.

We demonstrated that MSDC-0160 has strong, reproducible, positive effects across multiple models of Parkinson’s disease—it rescued dopamine-producing cells, improved behavioral deficits in mouse models and reversed inflammation. Overall, we believe it is a strong candidate for repurposing as a potential treatment that actually may slow the disease’s progression, rather than only mitigating symptoms.

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Deep Brain Stimulation Improves Parkinson’s Symptoms In Some Patients With SPG 11 Mutations

MedicalResearch.com Interview with:

Adolfo Ramirez Zamora, MD Associate Professor of Neurology and Phyllis E. Dake Endowed Chair in Movement Disorders Department of Neurology Albany Medical College

Dr. Adolfo Ramirez Zamora

Adolfo Ramirez Zamora, MD
Associate Professor of Neurology and
Phyllis E. Dake Endowed Chair in Movement Disorders
Department of Neurology
Albany Medical College

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Patients with SPG 11 mutations can present with motor symptoms characterized by juvenile onset dystonia, Parkinsonism and lower extremity spasticity. Parkinsonism appears to be responsive to levodopa therapy early in the disease but treatment is complicated by the occurrence of motor fluctuations resembling parkinson disease. Patients have short duration of medication effects, unpredictable response to medications along with generalized, excessive involuntary movements known as dyskinesias.

Deep Brain stimulation is a well-established treatment for movement disorders but it has never been used in this disease. We first report the clinical outcome obtained with globus pallidus internal deep brain stimulation in a patient with parkinsonism, dystonia, dyskinesias related to SPG 11. Additionally, we report for the first time the basal ganglia changes observed in the disease using intraoperative neuronal recordings. Patient had a sustained and remarkable response to stimulation over the next two years without side effects. Neurophysiologic changes revealed a unique pattern of neuronal firing despite of the resemblance to advance Parkinsons disease.

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Rosa & Co. Develop PhysioMap To Advance Drug Development Programs

MedicalResearch.com Interview with:
Rosa & Co. LLC,Dr. Christina Friedrich
Chief Engineer, PhysioPD
Rosa & Co. LLC

MedicalResearch.com: What is the background for this study?

Response: Elan was developing compounds for the treatment of Parkinson’s Disease. The compounds were designed to modify negative effects of alpha-synuclein on neurotransmitter vesicle trafficking, but these effects are poorly understood. Elan and Rosa collaborated in the development of a Synuclein PhysioMap®, a graphical model architecture to support hypothesis generation and testing. The objectives of the project were to provide insight into alpha-synuclein function in vesicle trafficking, memorialize and communicate the current state of knowledge within Elan, and to recommend experiments to test hypotheses, resolve uncertainties and identify and prioritize potential targets.

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Parkinson’s Disease Linked To Increase in Number of Inflammatory Markers

MedicalResearch.com Interview with:

Yong Cheng, PhD, post-doc fellow Section on Cellular Neurobiology Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health Bethesda, Maryland

Dr. Yong Cheng

Yong Cheng, PhD, post-doc fellow
Section on Cellular Neurobiology
Eunice Kennedy Shriver National Institute of Child Health and Human Development
National Institutes of Health
Bethesda, Maryland

MedicalResearch.com: What is the background for this study?

Response: Parkinson’s disease is the second most neurodegenerative disease after Alzheimer’s disease. The symptoms of the disease are typically movement related. However, the nonmotor features in PD are increasingly recognized. Evidence suggests that inflammation may play a role in the development of AD, and a substantial number of studies have demonstrated altered levels of peripheral blood inflammatory cytokines in patients with  Parkinson’s disease, but findings have been inconsistent for individual cytokines and between studies. Therefore, we undertook a systematic review of the scientific literature, using a meta-analysis to quantitatively summarize clinical data on blood cytokine levels in patients with PD, compared with healthy controls.

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Promising Study Evaluates Chemotherapy for Parkinson’s and Lewy Body Dementia

MedicalResearch.com Interview with:

Charbel Moussa MD. PhD Assistant Professor of Neurology Director- Laboratory for Dementia and Parkinsonism Clinical Research Director- National Parkinson's Foundation Center for Excellence Translational Neurotherapeutics Program Department of Neurology Georgetown University Medical Center Washington DC.

Dr. Charbel Moussa

Charbel Moussa MD. PhD
Assistant Professor of Neurology
Director- Laboratory for Dementia and Parkinsonism
Clinical Research Director- National Parkinson’s Foundation Center for Excellence
Translational Neurotherapeutics Program
Department of Neurology
Georgetown University Medical Center
Washington DC.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We conducted a pilot open label proof-of-concept study to evaluate the safety and tolerability of Nilotinib in participants with advanced Parkinson’s disease (PD) with dementia (PDD) or dementia with Lewy bodies (DLB). Our primary objective is to demonstrate that low oral daily doses of 150mg or 300mg Nilotinib (compared to 600-800mg in cancer) are safe and tolerated.

Our secondary objectives are that Nilotinib will cross the blood brain barier and may inhibit cerebral spinal fluid Abl. Based on preclinical data we also hypothesized that Nilotinib will increase DA levels. Motor and cognitive functions were also measured as exploratory clinical outcomes. Other exploratory outcomes are that Nilotinib may alter PD-related CSF biomarkers DJ-1 and α-synuclein. As most participants in this study had dementia we also explored the effects of Nilotinib on Alzheimer’s Disease-related CSF biomarkers, including Aβ40 and Aβ42, total tau and phosphorylated tau (p-tau).

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Single Head Injury Linked To Parkinson’s but Not Alzheimer’s Disease

MedicalResearch.com Interview with:

Paul K. Crane, MD MPH Professor Department of Medicine Adjunct Professor Department of Health Services University of Washington

Dr. Paul Crane

Paul K. Crane, MD MPH Professor
Department of Medicine Adjunct Professor
Department of Health Services
University of Washington

MedicalResearch.com: What is the background for this study?

Response: The background is that the most common experience of head injury with loss of consciousness is an apparent recovery. Sometimes this is very fast, sometimes it takes somewhat longer, but typically people return to their prior baseline. Nevertheless there is concern that the head injury may have set in motion processes that would lead to late life neurodegenerative conditions. Previous research has focused especially on Alzheimer’s disease. A more limited research has focused on Parkinson’s disease.

We used data from three prospective cohort studies that included more than 7,000 people to study the relationship between head injury with loss of consciousness and subsequent risk of Alzheimer’s and Parkinson’s disease. We collected head injury exposure data at study enrollment, at a time when we administered cognitive tests and knew they did not have dementia, so our exposure data are not biased. Each of these studies also performed brain autopsies on people who died, and we evaluated data from more than 1500 autopsies.

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No Increased Risk of Parkinson’s From MRI Gadolinium Exposure

MedicalResearch.com Interview with:

Blayne Welk, MD, MSc,FRCSC Assistant Professor of Surgery Western University London, Canada

Dr. Blayne Welk

Blayne Welk, MD, MSc,FRCSC
Assistant Professor of Surgery
Western University
London, Canada

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Prior research has demonstrated that gadolinium, which may be used during MRI scans to help visualise the body organs, can be deposited in the body, and remain there for years. The US FDA released a notice last year stating that further research was needed to evaluate the clinical implications of these brain deposits. One of the areas that gadolinium is deposited is the brain, specifically in two regions which control voluntary movement (the globus pallidus and dentate nucleus). Damage to these areas could cause symptoms of Parkinsonism. We used administrative data from Ontario, Canada to evaluate whether people who underwent MRI scans with gadolinium had a higher risk of developing Parkinsonism in the future. In this study, we did not demonstrate an increased risk of Parkinsonism in patients exposed to gadolinium.

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Rosacea Should Be Considered More Than Cosmetic Disorder

MedicalResearch.com Interview with:

Alexander Egeberg, MD PhD National Allergy Research Centre, Departments of Dermato-Allergology and Cardiology Herlev and Gentofte University Hospital, University of Copenhagen Hellerup, Denmark

Dr. Alexander Egeberg

Alexander Egeberg, MD PhD
National Allergy Research Centre, Departments of Dermato-Allergology and Cardiology
Herlev and Gentofte University Hospital
University of Copenhagen
Hellerup, Denmark 

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Egeberg: Rosacea skin shows an up-regulation of various cytokines (small proteins that are important in cell signalling), and displays increased activation and expression of matrix metalloproteinases (MMPs). Both rosacea and Parkinson’s disease have been associated with small intestinal bacterial overgrowth and Helicobacter pylori infection, and MMPs. MMPs are enzymes that are involved in tissue remodeling, organ development, and regulation of inflammatory processes.

Parkinson’s is a progressive neurological disease that results from the gradual loss of brain cells that produce dopamine, a chemical that sends messages to the part of the brain that controls movement and coordination. Importantly, MMPs have also been implicated in the pathogenesis of Parkinson’s disease and other neurodegenerative disorders, and MMPs contribute to loss of dopamine producing brain cells.

Rosacea is often characterized by flare-ups and remissions and typically presents as a redness on the cheeks, nose, chin or forehead. In our study, we found a significantly (approximately two-fold) increased risk of developing Parkinson’s disease, a chronic and progressive movement disorder, among patients with rosacea. Also, we found that treatment with tetracycline, an oral antibiotic, was associated with a slightly decreased risk of Parkinson’s disease.

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Hip Fractures and Falls Increase Years Before Parkinson’s disease Diagnosed

MedicalResearch.com Interview with:

Helena Nyström MD, PhD Candidate Department of Community Medicine and Rehabilitation Umeå University Umeå, Sweden

Helena Nyström

Helena Nyström MD, PhD Candidate
Department of Community Medicine and Rehabilitation
Umeå University
Umeå, Sweden

Medical Research: What is the background for this study?

Response: Parkinson’s disease (PD) has an insidious onset and the prodromal phase, preceding the onset of the characteristic PD symptoms, may last for decades. Most prodromal signs previously reported are of non-motor type, such as sleep and mood disorders. However, recent studies have reported balance problems and an increased risk of accidental injuries in the last 3-5 years before diagnosis of Parkinson’s disease , and in a previous study we found a lower muscle strength at military conscription in men who were diagnosed with  Parkinson’s disease three decades later. In this study, we aimed to investigate if such subtle strength deficits may translate into an increased risk of fall-related injuries.

Medical Research: What are the main findings?

Response: The median study time was 20 years before the diagnosis of  Parkinson’s disease , and during this time more individuals with PD (18%) than controls (11.5%) had at least one fall-related injury. The risk was most increased in the last few years before the diagnosis of  Parkinson’s disease , but a difference between the groups appeared already a decade before the PD diagnosis. The risk of hip fracture was increased during the entire study time of 26 years before the diagnosis of Parkinson’s disease .

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Parkinson’s Disease: No Benefit from Physical Therapy in Mild to Moderate Disease

Professor Carl E Clarke Professor of Clinical Neurology and Honorary Consultant Neurologist Department of Neurology City Hospital Sandwell and West Birmingham Hospitals NHS Trust Birmingham UK

Prof. Carl Clarke

More Interviews on Neurological Disorders on MedicalResearch.com
MedicalResearch.com Interview with:
Professor Carl E Clarke
Professor of Clinical Neurology and Honorary Consultant Neurologist Department of Neurology City Hospital
Sandwell and West Birmingham Hospitals NHS Trust
Birmingham UK 

Medical Research: What is the background for this study?  

Dr. ClarkeParkinson’s disease causes problems with activities of daily living that are only partially treated by medication and occasionally surgery. Physiotherapy and occupational therapy are traditionally used later in the disease, but it is unclear whether they are clinically and cost-effective in Parkinson’s disease.

Medical Research:   What are the main findings?

Dr. ClarkeWe performed a large pragmatic randomised trial to evaluate the clinical and cost-effectiveness of individualized physiotherapy and occupational therapy in Parkinson’s disease. The PD REHAB trial was a multicenter, open label, parallel group, controlled efficacy trial. 762 patients with mild-moderate Parkinson’s disease were recruited from 38 sites across the United Kingdom. For patients with mild to moderate Parkinson disease, there were no clinically meaningful benefits in activities of daily living or quality of life associated with physiotherapy and occupational therapy.

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Parkinson’s Drug L-DOPA May Protect Against Macular Degeneration

Brian S. McKay, Ph.D Associate Professor Department of Ophthalmology and Vision Science University of Arizona Medical Research Building, Room 212 Tucson, AZ 85724

Dr. McKay

MedicalResearch.com Interview with:
Brian S. McKay, Ph.D

Associate Professor
Department of Ophthalmology and Vision Science
University of Arizona
Medical Research Building, Room 212
Tucson, AZ 85724 

Medical Research: What is the background for this study?

Dr. McKay: AMD (age-related macular degeneration) is a disease that is race-related. White people get the disease and lose vision to AMD at much higher rate than Blacks or Hispanics.

Thus, while race is complex, pigmentation may protect from the disease. With this starting point, my laboratory went after the pigmentation pathway to determine how pigment may affect photoreceptor (the retinal cells that actually catch the light) survival. The  pigmented cells in the back of the eye are the retinal pigment epithelial cells (RPE), the rest of the retina does not pigment, it is clear not brown. We discovered that when the RPE make pigment they turn on molecular pathways to foster photoreceptor survival. Next we discovered the ligand for a receptor on the RPE that was tied to governing photoreceptor survival and pigmentation. That ligand was L-DOPA.

Knowing that L-DOPA is given to many aging individuals (those at risk of AMD), we developed a team to ask whether those taking L-DOPA for movement disorders are protected from AMD.

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Selective Targeting Can Improve Deep Brain Stimulation For Parkinson’s

Dr. Ilse S. Pienaar Honorary Lecturer in Neuroscience at Imperial College London (& Snr. Lecturer in Cellular Pathology, Northumbria University) Centre for Neuroinflammation & Neurodegeneration Division of Brain Sciences Faculty of Medicine Imperial College London Hammersmith Hospital Campus London United KingdomMedicalResearch.com Interview with:
Dr. Ilse S. Pienaar

Honorary Lecturer in Neuroscience at Imperial College London
(& Snr. Lecturer in Cellular Pathology, Northumbria University)
Centre for Neuroinflammation & Neurodegeneration
Division of Brain Sciences Faculty of Medicine
Imperial College London
Hammersmith Hospital Campus
London United Kingdom

 

Medical Research: What is the background for this study? What are the main findings?

Dr. Pienaar: A highly heterogeneous brainstem structure, the pedunculopontine nucleus (PPN) has been deemed a promising target for the delivery of deep-brain stimulation (DBS), to alleviate aspects of Parkinson’s disease (PD), especially gait and postural instability. However, optimal therapeutic targeting of the PPN has been hampered due to DBS being unable to discriminate between cell types being targeted. We optomised a novel technique, Designer Receptors Exclusively Activated by Designer Drugs (DREADD) in a rat model of PD, by which to target only the PPN cholinergic neurons. A series of behavioral tests revealed that selective stimulation of the PPN cholinergics completely reverses gait problems and postural instability in the PD rats.

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Parkinson’s Disease Can Be Stratified Into Three Distinct Groups

Ron Postuma, MD, MSc Associate Professor Department of Neurology Montreal General Hospital Montreal, QuebecMedicalResearch.com Interview with:
Ron Postuma, MD, MSc
Associate Professor
Department of Neurology
Montreal General Hospital
Montreal, Quebec

Medical Research: What is the background for this study? What are the main findings?

Dr. Postuma: The background is that we often think about Parkinson’s Disease as a single disease.  However, every clinician knows that there is a great deal of variability from patient to patient.  If we can understand the main aspects that separate patients into groups, we can target therapy better.

The analysis used a semi-automated means to divide Parkinson’s patients into groups, using extensive information about motor and non-motor aspects of disease.  We found that the non-motor symptoms, especially cognition, sleep disorders, and blood pressure changes were the most powerful predictors of which group a patient would be in.  Based on these non-motor (and some motor aspects), the most accurate way to divide patients was into three groups – diffuse (many non-motor symptoms), pure motor, and intermediate (halfway between the other).  We then followed patients over time.  The diffuse group had, by far, the worse prognosis.  This was not only for the non-motor aspects, but the motor as well. Continue reading

Paring Easy Aerobics With Fast Paced Cognitive Tasks May Improve Exercise Intensity

Dr. Lori P. Altmann Department of Speech, Language, and Hearing Sciences Center for Movement Disorders and Neurorestoration University of Florida, Gainesville, FloridaMedicalResearch.com Interview with:
Dr. Lori P. Altmann
Department of Speech, Language, and Hearing Sciences
Center for Movement Disorders and Neurorestoration
University of Florida, Gainesville, Florida

Medical Research: What is the background for this study? What are the main findings?

Dr. Altmann: There are a multitude of studies from our labs and others examining the effects of doing a variety of different cognitive tasks while walking or while maintaining postural control, and the results across studies are consistent—motor performance usually declines.  These “dual task effects” are exaggerated in healthy older adults, and are even more pronounced in people with Parkinson disease (PD).  Our study investigated dual task effects during cycling in healthy older adults and people with Parkinson disease.  In contrast to most studies of this type which typically contrast dual task effects of two cognitive tasks, we used an array of 12 cognitive tasks of graded difficulty, from very very easy to extremely difficult.  One of our primary goals was to establish that the dual task effects were directly related to the difficulty of the cognitive task.

Our primary findings were that, instead of cycling slower when doing various cognitive task, both groups of participants sped up, and the amount they sped up was directly related to the difficulty of cognitive tasks.  In the easiest task, cycling speed increased by an average of about 25%, With some participants actually doubling their single task speed. There was no evidence that this increase in cycling speed came as a result of prioritizing cycling over the cognitive tasks, as scores on the cognitive tasks either remained the same or got slightly better.  Interestingly, people with Parkinson disease still showed faster cycling during the easiest tasks, but did not benefit as much from the dual task as the healthy adults.

We attribute our findings to arousal that is triggered by both the cycling and the cognitive tasks which increases attentional resources that can be used for both motor and cognitive processing.  We believe the findings haven’t been documented before because most studies use gait or balance as the motor tasks, and these are much more difficult tasks that demand more attentional resources, leading to the typical findings of dual task costs instead of dual task benefits. The decrease in dual task benefits experienced by people with Parkinson disease, we believe, is due to the effects of Parkinson disease on neurotransmitters.  Both cognitive and physiological arousal increase the production of dopamine and norepinephrine in the brain, and disease processes in Parkinson disease interfere with production of these neurotransmitters, thus limiting arousal-based increases in attentional resources.

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Study Finds No Link Between Head Injuries and Parkinson’s Disease

MedicalResearch.com Interview with:
Line Kenborg, MSc, PhD

Survivorship Unit
Danish Cancer Society Research Center
Copenhagen

Medical Research: What is the background for this study? What are the main findings?

Response: The hypothesis that head injuries increase the risk for Parkinson disease has been examined in many studies during the past decades, but the findings have been highly inconsistent. We have previously examined the hypothesis in a study based on information on head injuries and Parkinson disease from the Danish National Hospital Registry. In this study, we found a positive association between a hospital contact for a head injury in middle or late adulthood and a diagnosis of Parkinson disease. The reported association, however, was almost entirely due to injuries that occurred during the months preceding the first hospital contact for Parkinson disease. Because we used information from registries, we lacked detailed diagnostic information to distinguish Parkinson disease from other types of parkinsonism, and we had no information on milder head injuries and head injuries in early life. So we wanted to study whether head injuries throughout life increased the risk for Parkinson disease in the largest interview-based case-control study to date including patients with a verified diagnosis of Parkinson disease. The main finding of our study is that we do not find any association between head injuries and Parkinson disease.

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Parkinson’s Disease Associated With Altered Intestinal Bacteria

Filip Scheperjans MD Department of Neurology Helsinki University Central Hospital Department of Neurological Sciences University of Helsinki, Helsinki, FinlandMedicalResearch.com Interview with:
Filip Scheperjans MD

Department of Neurology
Helsinki University Central Hospital
Department of Neurological Sciences
University of Helsinki, Helsinki, Finland

Medical Research: What is the background for this study? What are the main findings?

Dr. Scheperjans: In Parkinson’s disease (PD), the first neurodegenerative changes are seen in the olfactory bulb and enteric nervous system. Correspondingly, most Parkinson’s disease patients suffer from hyposmia and gastrointestinal symptoms, frequently years before motor symptoms evolve. Therefore, it has been suggested that an environmental factor acting through the nose or gut, could be involved in Parkinson’s disease. Interestingly, those two habitats are where our body gets mostly exposed to environmental agents, including microbes. Previous attempts to identify microbes related to Parkinson’s disease pointed to Helicobacter pylori and small intestinal bacterial overgrowth, but in the end had been somewhat inconclusive. But there possibly was a signal. We saw next generation sequencing approaches as a new opportunity to revisit the microbe theory in PD. Studies of gut microbiome composition in neurodegenerative disease have not been published before, although alterations in gut microbiota have been demonstrated in many other diseases and gut microbiota are in close interaction with the central nervous system.

The fecal microbiome of Parkinson’s disease subjects clearly differed from that of matched controls and this difference was independent of the potential confounders that we assessed. The most significant finding was that the abundance of bacteria from the Prevotellaceae family was reduced by 78% in Parkinson’s disease patients. A low abundance of Prevotellaceae was 86% sensitive for PD, but rather unspecific. However, a combination of 4 bacterial families increased specificity for PD to 90%. So microbiome analysis performed quite well in distinguishing Parkinson’s disease patients from control subjects. Another interesting finding was that, within the Parkinson’s disease group, abundance of Enterobacteriaceae bacteria was related to the motor symptoms of patients. They were positively associated with the severity of postural instability and gait difficulty.
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Parkinson Disease: Naltrexone May Be Useful For Impulse Control

Associate Professor of Psychiatry and Neurology Perelman School of Medicine at the University of Pennsylvania Philadelphia, PA 19104-2676 Parkinson's Disease Research, Education and Clinical Center (PADRECC) Mental Illness Research, Education and Clinical Center (MIRECC) Philadelphia Veterans Affairs Medical CenterMedicalResearch.com Interview with:
Daniel Weintraub, M.D.
Associate Professor of Psychiatry and Neurology
Perelman School of Medicine at the University of Pennsylvania
Philadelphia, PA 19104-2676
Parkinson’s Disease Research, Education and Clinical Center (PADRECC)
Mental Illness Research, Education and Clinical Center (MIRECC)
Philadelphia Veterans Affairs Medical Center

Medical Research: What are the main findings of the study?

Dr. Weintraub: That there is mixed evidence for the efficacy of naltrexone in the treatment of impulse control disorders in Parkinson’s disease, and the evidence is sufficient to support further study of this compound class for this indication.  In addition, the study demonstrates that it is possible to conduct a clinical trial in this area.
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Parkinson’s Disease: Are Newer Meds Better Than Levodopa?

Richard Gray Professor of Medical Statistics Clinical Trial Service Unit Richard Doll Building, OxfordMedicalResearch Interview with:
Richard Gray
Professor of Medical Statistics
Clinical Trial Service Unit
Richard Doll Building, Oxford


MedicalResearch: What are the main findings of the study?

Prof. Gray: We found that, when we asked patients with Parkinson’s disease how their drugs affected their overall quality of life, the older drug levodopa was better than newer, more expensive drugs and that this benefit persisted for at least seven years from starting treatment.
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Parkinson’s Disease: Effect of Deep Brain Stimuation on Driving

Priv. Doz. Dr. Carsten Buhmann Department of Neurology University Medical Center Hamburg-Eppendorf, Hamburg, Germany.MedicalResearch.com Interview with:
Priv. Doz. Dr. Carsten Buhmann
Department of Neurology
University Medical Center Hamburg-Eppendorf
Hamburg, Germany.

MedicalResearch.com: What are the main findings of the study?

Answer: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) has no negative but rather a beneficial effect on driving in patients with Parkinsons´s disease (PD). Driving not only was superior in even more clinically affected PD patients with DBS compared with PD patients without DBS but also patients with DBS drove better with stimulation than with levodopa.

This might reflect favorable driving-relevant nonmotor effects due to STN-DBS.
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Parkinson’s Disease: Cognitive Impairment and Plasma Ceramides

Michelle M. Mielke, Ph.D. Associate Professor Department of Health Sciences Research Division of Epidemiology Mayo Clinic 200 First Street SW Rochester, MN 55905MedicalResearch.com: Interview with:

Michelle M. Mielke, Ph.D.
Associate Professor
Department of Health Sciences Research
Division of Epidemiology
Mayo Clinic 200 First Street SW
Rochester, MN 55905

MedicalResearch.com: What are the main findings of the study?

Dr. Mielke: Among Parkinson’s disease (PD) patients, plasma levels of ceramides and monohexylceramides were higher in patients with cognitive impairment or dementia compared to patients who were cognitively normal.  Levels of these lipids were also higher in the combined group of PD patients compared to non-PD controls but the number of controls were small.

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Dementia: Lewy Body vs Parkinson’s Disease

Rodolfo Savica, MD, MSc Department of Neurology, College of Medicine Division of Epidemiology, Department of Health Sciences Research, College of Medicine, Mayo Clinic, Rochester, MinnesotaMedicalResearch.com Interview with:
Rodolfo Savica, MD, MSc
Department of Neurology, College of Medicine
Division of Epidemiology, Department of Health Sciences Research, College of Medicine, Mayo Clinic, Rochester, Minnesota

 

MedicalResearch.com: What are the main findings of this study?

Dr. Savica: This study is the first in North America to explore the incidence of DLB and PDD in a population based sample. We found that the overall incidence of dementia with Lewy bodies (DLB), considered the second leading cause of neurodegenerative dementia after Alzheimer`s disease, is lower than that of Parkinson`s disease (PD), increases steeply with age, and is markedly higher in men than in women.
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Parkinson’s Disease: ApoA1 may be a Protection Marker

Alice Chen-Plotkin, MD Assistant Professor Department of Neurology University of Pennsylvania School of Medicine MedicalResearch.com: Interview with Alice Chen-Plotkin, MD
Assistant Professor
Department of Neurology
University of Pennsylvania School of Medicine

 


MedicalResearch.com: What are the main findings of the study?

Answer: Parkinson’s disease (PD) is an incurable neurodegenerative disease.  Many neurons die, but the neurons that make dopamine (dopaminergic neurons) are particularly vulnerable.  We think that the disease actually starts well before the time when people show clinical symptoms.  We were therefore interested in finding proteins from the blood that correlated with better or worse dopaminergic neuron integrity.  Since it’s hard to access the dopaminergic neurons directly, we looked at a tracer that labels the ends of the dopaminergic neurons in people who do not have Parkinson’s disease but are at high risk for developing it, and we also looked at the age at onset of PD in people who are already symptomatic.  Screening just under 100 different proteins from the blood, we found that higher plasma levels of apolipoprotein A1 (ApoA1) were correlated with better tracer uptake in the people who did not yet have PD, and with older ages at onset in the people who already had PD.  These data suggest that plasma ApoA1 may be a marker for PD risk, with higher levels being relatively protective.

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Parkinson’s Disease: Sudden Drop in Testosterone may Trigger Symptoms

 Kalipada Pahan, Ph.D.  The Floyd A. Davis, M.D., Endowed Chair of Neurology Professor Departments of Neurological Sciences, Biochemistry and Pharmacology Rush University Medical Center 1735 West Harrison St, Suite 320 Chicago, IL 60612MedicalResearch.com Interview with: Kalipada Pahan, Ph.D.

The Floyd A. Davis, M.D., Endowed Chair of Neurology
Professor
Departments of Neurological Sciences, Biochemistry and Pharmacology
Rush University Medical Center
1735 West Harrison St, Suite 320 Chicago, IL 60612

MedicalResearch.com: What are the main findings of the study?

Dr. Pahan: While different toxins and a number of complex genetic approaches are used to model Parkinson’s disease in mice, this study delineates that simple castration is sufficient to cause persistent Parkinson’s like pathology and symptoms in male mice. This simple, but persistent, model may be helpful in discovering drugs against Parkinson’s disease. Furthermore, these results suggest that sudden drop of testosterone level could trigger Parkinson’s disease.
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Parkinson’s disease and exposure to Pesticides

MedicalResearch.com eInterview with Dr. Emanuele Cereda

Nutrition and Dietetics Service, Fondazione IRCCS Policlinico San Matteo
Viale Golgi 19, 27100 Pavia, Italy

MedicalResearch.com: What are the main findings of the study?

Dr. Cereda: A large analysis of more than 100 studies shows that exposure to pesticides, or bug and weed killers, and solvents is likely associated with a higher risk of developing Parkinson’s disease.

MedicalResearch.com: Were any of the findings unexpected?

Dr. Cereda: In first instance I can say no as in every day clinical practice we frequently see patients reporting such exposure. Accordingly, it appears quite obvious to look at these exposures as risk factors. Unfortunately, from an epidemiologic point of view this is not enough! That’s why we did this study. Amazing rather than surprising was the fact that commonly the sources of funding in the studies we retrieved and included in meta-analysis were health or health-related institutions, private foundations (mainly Parkinosn’s disease foundations), or government or para-government companies. No study acknowledged the involvement of any chemicals manufacturer!
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